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Hereditary disorders of voluntary motor neurons are individually relatively uncommon, but have the potential to provide significant insights into motor neuron function in general and into the mechanisms underlying the more common form of sporadic Amyotrophic Lateral Sclerosis. Recently, mutations in a number of novel genes have been associated with Lower Motor Neuron (HSPB1, HSPB8, GARS, Dynactin), Upper Motor Neuron (Spastin, Atlastin, Paraplegin, HSP60, KIF5A, NIPA1) or mixed ALS-like phenotypes (Alsin, Senataxin, VAPB, BSCL2). In comparison to sporadic ALS these conditions are usually associated with slow progression, but as experience increases, a wide variation in clinical phenotype has become apparent. At the molecular level common themes are emerging that point to areas of specific vulnerability for motor neurons such as axonal transport, endosomal trafficking and RNA processing. We review the clinical and molecular features of this diverse group of genetically determined conditions and consider the implications for the broad group of motor neuron diseases in general.

Original publication




Journal article


Biochim Biophys Acta

Publication Date





986 - 1000


Adolescent, Adult, Amyotrophic Lateral Sclerosis, Animals, Axonal Transport, GTP-Binding Protein gamma Subunits, Heat-Shock Proteins, Humans, Mice, Mice, Transgenic, Models, Neurological, Motor Neuron Disease, Muscles, Mutation, Neoplasm Proteins, Phenotype, Signal Transduction, Syndrome